scholarly journals Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Taisuke Miyazaki ◽  
Megumi Morimoto-Tomita ◽  
Coralie Berthoux ◽  
Kotaro Konno ◽  
Yoav Noam ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Ectopic Expression ◽  
Inhibitory Neurons ◽  
Mammalian Brain ◽  
Neurotransmitter Receptors ◽  
Presynaptic Terminals ◽  
Postsynaptic Receptors ◽  
A Cell ◽  
Synaptic Mechanisms

Ionotropic neurotransmitter receptors at postsynapses mediate fast synaptic transmission upon binding of the neurotransmitter. Post- and trans-synaptic mechanisms through cytosolic, membrane, and secreted proteins have been proposed to localize neurotransmitter receptors at postsynapses. However, it remains unknown which mechanism is crucial to maintain neurotransmitter receptors at postsynapses. In this study, we ablated excitatory or inhibitory neurons in adult mouse brains in a cell-autonomous manner. Unexpectedly, we found that excitatory AMPA receptors remain at the postsynaptic density upon ablation of excitatory presynaptic terminals. In contrast, inhibitory GABAA receptors required inhibitory presynaptic terminals for their postsynaptic localization. Consistent with this finding, ectopic expression at excitatory presynapses of neurexin 3alpha, a putative trans-synaptic interactor with the native GABAA receptor complex, could recruit GABAA receptors to contacted postsynaptic sites. These results establish distinct mechanisms for the maintenance of excitatory and inhibitory postsynaptic receptors in the mature mammalian brain.

scholarly journals Morphological diversity and connectivity of hippocampal interneurons

2018 ◽  
Vol 373 (3) ◽  
pp. 619-641 ◽  
Author(s):  
Sam A. Booker ◽  
Imre Vida
Keyword(s):  
Morphological Diversity ◽  
Inhibitory Neurons ◽  
Mammalian Brain ◽  
Neuronal Function ◽  
Principal Cells ◽  
Axon Terminals ◽  
Efferent Connections ◽  
Rich Diversity ◽  
A Cell ◽  
The Rich

Abstract The mammalian forebrain is constructed from ensembles of neurons that form local microcircuits giving rise to the exquisite cognitive tasks the mammalian brain can perform. Hippocampal neuronal circuits comprise populations of relatively homogenous excitatory neurons, principal cells and exceedingly heterogeneous inhibitory neurons, the interneurons. Interneurons release GABA from their axon terminals and are capable of controlling excitability in every cellular compartment of principal cells and interneurons alike; thus, they provide a brake on excess activity, control the timing of neuronal discharge and provide modulation of synaptic transmission. The dendritic and axonal morphology of interneurons, as well as their afferent and efferent connections within hippocampal circuits, is central to their ability to differentially control excitability, in a cell-type- and compartment-specific manner. This review aims to provide an up-to-date compendium of described hippocampal interneuron subtypes, with respect to their morphology, connectivity, neurochemistry and physiology, a full understanding of which will in time help to explain the rich diversity of neuronal function.

scholarly journals Tau protein function in living cells.

1986 ◽  
Vol 103 (6) ◽  
pp. 2739-2746 ◽  
Author(s):  
D G Drubin ◽  
M W Kirschner
Keyword(s):  
Tau Protein ◽  
Protein Function ◽  
Mammalian Brain ◽  
Protein Activity ◽  
Neuronal Morphogenesis ◽  
Microtubule Polymerization ◽  
A Cell ◽  
Nerve Cell Differentiation

Tau protein from mammalian brain promotes microtubule polymerization in vitro and is induced during nerve cell differentiation. However, the effects of tau or any other microtubule-associated protein on tubulin assembly within cells are presently unknown. We have tested tau protein activity in vivo by microinjection into a cell type that has no endogenous tau protein. Immunofluorescence shows that tau protein microinjected into fibroblast cells associates specifically with microtubules. The injected tau protein increases tubulin polymerization and stabilizes microtubules against depolymerization. This increased polymerization does not, however, cause major changes in cell morphology or microtubule arrangement. Thus, tau protein acts in vivo primarily to induce tubulin assembly and stabilize microtubules, activities that may be necessary, but not sufficient, for neuronal morphogenesis.

scholarly journals A molecular logic of sensory coding revealed by optical tagging of physiologically-defined neuronal types

2019 ◽  
Author(s):  
Donghoon Lee ◽  
Maiko Kume ◽  
Timothy E Holy
Keyword(s):  
Neural Circuit ◽  
Strong Predictor ◽  
Ectopic Expression ◽  
Cell Types ◽  
Specific Cell ◽  
Molecular Logic ◽  
Neuronal Types ◽  
A Cell ◽  
Circuit Function

Neural circuit analysis relies on having molecular markers for specific cell types. However, for a cell type identified only by its circuit function, the process of identifying markers remains laborious. Here, we report physiological optical tagging sequencing (PhOTseq), a technique for tagging and expression-profiling cells based on their functional properties. We demonstrate that PhOTseq is capable of selecting rare cell types and enriching them by nearly one hundred-fold. We applied PhOTseq to the challenge of mapping receptor-ligand pairings among vomeronasal pheromone-sensing neurons in mice. Together with in vivo ectopic expression of vomeronasal chemoreceptors, PhOTseq identified the complete combinatorial receptor code for a specific set of ligands, and revealed that the primary sequence of a chemoreceptor was an unexpectedly strong predictor of functional similarity.

scholarly journals In vivo imaging of injured cortical axons reveals a rapid onset form of Wallerian degeneration

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Alison Jane Canty ◽  
Johanna Sara Jackson ◽  
Lieven Huang ◽  
Antonio Trabalza ◽  
Cher Bass ◽  
...  
Keyword(s):  
Nervous System ◽  
Wallerian Degeneration ◽  
Molecular Mechanisms ◽  
Rapid Onset ◽  
Spatiotemporal Dynamics ◽  
Myelinated Fibre ◽  
Mammalian Brain ◽  
Axon Loss ◽  
Synaptic Mechanisms

Abstract Background Despite the widespread occurrence of axon and synaptic loss in the injured and diseased nervous system, the cellular and molecular mechanisms of these key degenerative processes remain incompletely understood. Wallerian degeneration (WD) is a tightly regulated form of axon loss after injury, which has been intensively studied in large myelinated fibre tracts of the spinal cord, optic nerve and peripheral nervous system (PNS). Fewer studies, however, have focused on WD in the complex neuronal circuits of the mammalian brain, and these were mainly based on conventional endpoint histological methods. Post-mortem analysis, however, cannot capture the exact sequence of events nor can it evaluate the influence of elaborated arborisation and synaptic architecture on the degeneration process, due to the non-synchronous and variable nature of WD across individual axons. Results To gain a comprehensive picture of the spatiotemporal dynamics and synaptic mechanisms of WD in the nervous system, we identify the factors that regulate WD within the mouse cerebral cortex. We combined single-axon-resolution multiphoton imaging with laser microsurgery through a cranial window and a fluorescent membrane reporter. Longitudinal imaging of > 150 individually injured excitatory cortical axons revealed a threshold length below which injured axons consistently underwent a rapid-onset form of WD (roWD). roWD started on average 20 times earlier and was executed 3 times slower than WD described in other regions of the nervous system. Cortical axon WD and roWD were dependent on synaptic density, but independent of axon complexity. Finally, pharmacological and genetic manipulations showed that a nicotinamide adenine dinucleotide (NAD+)-dependent pathway could delay cortical roWD independent of transcription in the damaged neurons, demonstrating further conservation of the molecular mechanisms controlling WD in different areas of the mammalian nervous system. Conclusions Our data illustrate how in vivo time-lapse imaging can provide new insights into the spatiotemporal dynamics and synaptic mechanisms of axon loss and assess therapeutic interventions in the injured mammalian brain.

scholarly journals Sensory coding mechanisms revealed by optical tagging of physiologically defined neuronal types

Science ◽  
2019 ◽  
Vol 366 (6471) ◽  
pp. 1384-1389 ◽  
Author(s):  
Donghoon Lee ◽  
Maiko Kume ◽  
Timothy E. Holy
Keyword(s):  
Neural Circuit ◽  
Ectopic Expression ◽  
Cell Types ◽  
Specific Cell ◽  
Sensory Coding ◽  
Cell Type ◽  
Neuronal Types ◽  
A Cell ◽  
Circuit Function

Neural circuit analysis relies on having molecular markers for specific cell types. However, for a cell type identified only by its circuit function, the process of identifying markers remains laborious. We developed physiological optical tagging sequencing (PhOTseq), a technique for tagging and expression profiling of cells on the basis of their functional properties. PhOTseq was capable of selecting rare cell types and enriching them by nearly 100-fold. We applied PhOTseq to the challenge of mapping receptor-ligand pairings among pheromone-sensing neurons in mice. Together with in vivo ectopic expression of vomeronasal chemoreceptors, PhOTseq identified the complete combinatorial receptor code for a specific set of ligands.

Ultrastructure of melanocyte-keratinocyte interactions and pigment transfer in vitro

1978 ◽  
Vol 36 (2) ◽  
pp. 650-651
Author(s):  
Raul I. Garcia ◽  
Evelyn A. Flynn ◽  
George Szabo
Keyword(s):  
Direct Injection ◽  
Skin Pigmentation ◽  
Freeze Fracture ◽  
Pigment Granule ◽  
Time Lapse ◽  
Ultrastructural Level ◽  
Lanthanum Tracer ◽  
A Cell

Skin pigmentation in mammals involves the interaction of epidermal melanocytes and keratinocytes in the structural and functional unit known as the Epidermal Melanin Unit. Melanocytes(M) synthesize melanin within specialized membrane-bound organelles, the melanosome or pigment granule. These are subsequently transferred by way of M dendrites to keratinocytes(K) by a mechanism still to be clearly defined. Three different, though not necessarily mutually exclusive, mechanisms of melanosome transfer have been proposed: cytophagocytosis by K of M dendrite tips containing melanosomes, direct injection of melanosomes into the K cytoplasm through a cell-to-cell pore or communicating channel formed by localized fusion of M and K cell membranes, release of melanosomes into the extracellular space(ECS) by exocytosis followed by K uptake using conventional phagocytosis. Variability in methods of transfer has been noted both in vivo and in vitro and there is evidence in support of each transfer mechanism. We Have previously studied M-K interactions in vitro using time-lapse cinemicrography and in vivo at the ultrastructural level using lanthanum tracer and freeze-fracture.

Analysis of the Dynamics of the Electric Capacitance of a Cell Monolayer at the Late Stages of Caco-2 cell Differentiation

2019 ◽  
Vol 35 (6) ◽  
pp. 87-90
Author(s):  
S.V. Nikulin ◽  
V.A. Petrov ◽  
D.A. Sakharov
Keyword(s):  
Impedance Spectroscopy ◽  
Cell Monolayer ◽  
Microfluidic Chips ◽  
Russian Science ◽  
Electric Capacitance ◽  
A Cell ◽  
Static Conditions ◽  
Late Stages

The real-time monitoring of electric capacitance (impedance spectroscopy) allowed obtaining evidence that structures which look like intestinal villi can be formed during the cultivation under static conditions as well as during the cultivation in microfluidic chips. It was shown in this work via transcriptome analysis that the Hh signaling pathway is involved in the formation of villus-like structures in vitro, which was previously shown for their formation in vivo. impedance spectroscopy, intestine, villi, electric capacitance, Hh The study was funded by the Russian Science Foundation (Project 16-19-10597).

scholarly journals TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
You Shuai ◽  
Zhonghua Ma ◽  
Weitao Liu ◽  
Tao Yu ◽  
Changsheng Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Mechanistic Model ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Reporter Assays

Abstract Background Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms. Methods LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays. Results It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions. Conclusions Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.

scholarly journals In vivo targeting of lentiviral vectors pseudotyped with the Tupaia paramyxovirus H glycoprotein bearing a cell-specific ligand

2021 ◽  
Author(s):  
Takele Argaw ◽  
Michael P. Marino ◽  
Andrew Timmons ◽  
Lindsey Eldridge ◽  
Kazuyo Takeda ◽  
...  
Keyword(s):  
Lentiviral Vectors ◽  
A Cell ◽  
Specific Ligand
Sign in / Sign up

Export Citation Format

Share Document